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Aclarubicin (aclacinomycin A) is one of the anthracycline antineoplastic antibiotics with a multifaceted mechanism of antitumor activity. As a second-generation drug, it offers several advantages compared to standard anthracycline drugs such as doxorubicin or daunorubicin, which could position it as a potential blockbuster drug in antitumor therapy. Key mechanisms of action for aclarubicin include the inhibition of both types of topoisomerases, suppression of tumor invasion processes, generation of reactive oxygen species, inhibition of chymotrypsin-like activity, influence on cisplatin degradation, and inhibition of angiogenesis. Therefore, aclarubicin appears to be an ideal candidate for antitumor therapy. However, despite initial interest in its clinical applications, only a limited number of high-quality trials have been conducted thus far. Aclarubicin has primarily been evaluated as an induction therapy in acute myeloid and lymphoblastic leukemia. Studies have indicated that aclarubicin may hold significant promise for combination therapies with other anticancer drugs, although further research is needed to confirm its potential. This paper provides an in-depth exploration of aclarubicin's diverse mechanisms of action, its pharmacokinetics, potential toxicity, and the clinical trials in which it has been investigated. [ABSTRACT FROM AUTHOR]

Chemotherapy is a common and effective treatment for cancer, but these drugs are also associated with significant side effects affecting patients' well‐being. One such debilitating side effect is mucositis, characterized by inflammation, ulcerations, and altered physiological functions of the gastrointestinal (GI) tract's mucosal lining. Understanding the mechanisms of chemotherapy‐induced intestinal mucositis (CIM) is crucial for developing effective preventive measures and supportive care. Chemotherapeutics not only target cancer cells but also rapidly dividing cells in the GI tract. These drugs disrupt endoplasmic reticulum (ER) homeostasis, leading to ER‐stress and activation of the unfolded protein response (UPR) in various intestinal epithelial cell types. The UPR triggers signaling pathways that exacerbate tissue inflammation and damage, influence the differentiation and fate of intestinal epithelial cells, and compromise the integrity of the intestinal mucosal barrier. These factors contribute significantly to mucositis development and progression. In this review, we aim to give an in‐depth overview of the role of ER‐stress in mucositis and its impact on GI function. This will provide valuable insights into the underlying mechanisms and highlighting potential therapeutic interventions that could improve treatment‐outcomes and the quality of life of cancer patients. [ABSTRACT FROM AUTHOR]

Cancer therapy-related cardiovascular toxicity (CTR-CVT) is gradually becoming a critical factor affecting the prognosis of cancer survivors. Vascular endothelial growth factor (VEGF) and its receptor inhibitors (VEGFIs), developed as novel anti-cancer drugs targeting VEGF, are now widely used in clinical practice. They can extend the survival period of the cancer patients and improve the prognosis of the patients. However, the hypertension induced by VEGFIs, as the most common CTR-CVT, may limit and impact their use and leads to severe cardiovascular diseases (CVD). It is essential to closely monitor blood pressure in the cancer patients treated with VEGFIs, conduct early assessments, and optimize the management to achieve the best anti-cancer efficacy and minimize the risk of CTR-CVT. This review discusses the clinical manifestations, pathogenesis, diagnosis, and treatment strategies of VEGFIs-related hypertension, in order to provide better guidances for managing and addressing VEGFIs-related hypertension for the clinicians. [ABSTRACT FROM AUTHOR]

Purpose: Pulmonary fibrosis (PF) is a severe, progressive disease, which may be caused by exposure to certain medications. Methods: We queried the U.S. FDA Adverse Event Reporting System (FAERS) from 2000 to 2022, using the search terms "pulmonary fibrosis" and "idiopathic pulmonary fibrosis" and excluded reports with patients under the age of 18 years, and patients with unknown sex or age. Reports were sorted by generic drug names, counted, and plotted over time using a best‐fit trendline based on an exponential function. Results: From 2000 to 2022, there were 24 095 935 adverse drug events reported in FAERS, of which 17 520 (0.07%) were reported as PF. After excluding reports containing patients with unknown age (5255, 30%), sex (122, 0.7%), and age below 18 years old (155, 0.9%), our study included 11 988 reports. The mean age of the study sample was 66.5 ± 13.1 years, and 6248 patients (52.1%) were male. Plotting the 11 988 reports by year revealed an exponential best fit line (R2 = 0.88) with a positive slope over time. The top five drug classes associated with PF were disease modifying antirheumatic drugs (DMARDs, 39.4%), antineoplastic agents (26.4%), cardiovascular agents (12.6%), corticosteroids (4.6%), and immunosuppressive agents (4.0%). Conclusion: A 23‐year analysis of the FAERS database revealed exponentially increasing adverse event reports of PF. Significant annual increases in reporting of PF suspected with DMARDs and antineoplastic agents were identified. Our study highlights important trends, which should be used to guide PF research related to drugs of potential importance. [ABSTRACT FROM AUTHOR]

The occupational exposure of caregivers to antineoplastic agents has been demonstrated since 1979. Since the early 1990s, numerous studies from several countries have demonstrated the contamination of care facilities by antineoplastic drugs. As it is easier to sample, most contamination measurements in workers are carried out in urine sample. The distribution and elimination half‐lives of irinotecan suggest that blood can be considered as better than urine for the biomonitoring of a potential contamination of healthcare workers. We describe here the development and the validation of a UHPLC–MS/MS method to simultaneously quantify irinotecan, and two of its main metabolites, APC and SN‐38, at ultra‐trace levels in plasma and red blood cells (RBC). This method has been applied to blood samples collected from several healthcare services in a French comprehensive cancer center. The results demonstrate that the method is sensitive enough to identify a contamination of healthcare workers by irinotecan and SN‐38 at very low concentrations. Moreover, the results show that analysis of RBC is of great interest and complementary to that of serum. [ABSTRACT FROM AUTHOR]

Resulted from the severe side effects, the development of inexpensive, simple and sensitive method for amethopterin (ATP, an antineoplastic drug) is very important but it still remains a challenge. In this work, low cost nanohybrid composed of carbon nanobowl (CNB) and β-cyclodextrins (β-CD) (CNB-CD) was prepared with a simple autopolymerization way and applied as electrode material to develop a novel electrochemical sensor of ATP. Scanning-/transmission-electron microscopy, Fourier transform infrared spectrum, photographic image and electrochemical technologies were utilized to characterize morphologies and structure of the as-prepared CNB and CNB-CD materials. On the basic of the coordination advantages from CNB (prominent electrical property and surface area) and β-CD (superior molecule-recognition and solubility capabilities), the CNB-CD nanohybrid modified electrode exhibits superior sensing performances toward ATP, and a low detection limit of 0.002 μM coupled with larger linearity of 0.005–12.0 μM are obtained. In addition, the as-prepared sensor offers desirable repeatability, stability, selectivity and practical application property, confirming that this proposal may have important applications in the determination of ATP.

Surveillance for environmental contamination of antineoplastic drugs has been recommended by authoritative bodies such as the United States Pharmacopeia and the National Association of Pharmacy Regulatory Authorities. Clear guidance is needed on how to develop sampling strategies that align with surveillance objectives efficiently and effectively. We conducted a series of simulations using previously collected surveillance data from nine cancer treatment centers to evaluate different sampling strategies. We evaluated the impact of sampling 2, 5, 10, or 20 surfaces, at monthly, quarterly, semi-annual, and annual frequencies, while employing either a random or sentinel surface selection strategy to assess contamination by a single antineoplastic drug (AD) or by a panel of three ADs. We applied two different benchmarks: a binary benchmark of above or below the limit of detection and AD-specific hygienic guidance values, based on 90th percentile values as quantitative benchmarks. The use of sentinel surfaces to evaluate a three-drug panel relative to 90th percentile hygienic guidance values (HGVs) resulted in the most efficient and effective surveillance strategy. [ABSTRACT FROM AUTHOR]

Abstract To evaluate the effects of safe‐handling education on the cognition, practice and stress handling of antineoplastic drugs in clinical nurses. This study uses a quasi‐experimental, non‐equivalent control group pre‐test and post‐test design. The experimental and control groups had 30 nurses each, who handled antineoplastic drugs from three institutions. This study examines the safe handling of antineoplastic drugs six times, for two hours each over two weeks. To verify the homogeneity of the experimental and control groups and the effectiveness of safe‐handling education about antineoplastic drugs, a chi‐square test and independent samples t‐test were performed. The results were statistically significant in both groups (cognition [t = 6.84, p

The high performance thin layer chromatography method described here enables simple, accurate and precise estimation of alectinib hydrochloride content in capsule formulation. To achieve adequate separation, G60 - F254 pre-coated silica gel sheets of aluminium were used as the stationary phase. A mobile phase comprising a solvent mixture of methanol and water in a ratio of 80:20 (V/V) was utilized with a chamber saturation duration of 30 minutes. The retardation factor value was found to be 0.47 at the detection wavelength 341 nm. The method's linearity was confirmed across a concentration range from 600 - 2100 ng band-1, exhibiting a high correlation coefficient of 0.9992. The accuracy range was observed between 98.50 % - 100.45 %. The lowest detection limits of drug were observed to be 17.49 ng band-1 and lowest quantitation limits of drug were found to be 53.01 ng band-1. This developed methodology was effectively employed for the quantification of alectinib hydrochloride in capsule preparations. [ABSTRACT FROM AUTHOR]

Objective: Antineoplastic drugs (ADs) are widely used in clinical practice and have been demonstrated to be effective in treating malignant tumors. However, they carry a risk of cytogenotoxicity for healthcare workers. Studies have reported that genotoxic biomarkers can be applied to assess the occupational health status of healthcare workers at an early stage, but results of different studies are variable. The objectives of the review were examine the association between long-term exposure to ADs and cytogenetic damage to healthcare workers. Methods: We systematically reviewed studies between 2005 and 2021 using PubMed, Embase and Web of Science databases that used cytogenetic biomarkers to assess occupational exposure to ADs in healthcare workers. We used RevMan5.4 to analyze the tail length parameters of the DNA, frequency of the chromosomal aberrations, sister chromatid exchanges and micronuclei. A total of 16 studies were included in our study. The studies evaluate the quality of the literature through the Agency for Healthcare Research and Quality. Results: The results revealed that under the random-effects model, the estimated standard deviation was 2.37 (95% confidence interval [CI] 0.92–3.81, P = 0.001) for the tail length parameters of the DNA, 1.48 (95% CI 0.71–2.25, P = 0.0002) for the frequency of chromosomal aberrations, 1.74 (95% CI 0.49–2.99, P = 0.006) for the frequency of sister chromatid exchanges and 1.64 (95% CI 0.83–2.45, P < 0.0001) for the frequency of micronuclei. Conclusions: The results indicate that there is a significant association between occupational exposure to ADs and cytogenetic damage, to which healthcare workers should be alerted. [ABSTRACT FROM AUTHOR]

With increasing numbers of cancer cases, the use of antineoplastic agents is expected to rise. This will be accompanied by an increase in occupational exposure, which can cause unwanted health effects in workers. Our aim was to give an overview of genotoxic and epigenetic effects after occupational exposure to antineoplastic agents and to assess the concentration−effect relation. Four databases were searched for papers investigating genotoxic and/or epigenetic effects of occupational exposure to antineoplastic agents. Out of the 245 retrieved papers, 62 were included in this review. In this systematic literature review, we confirmed that exposure of healthcare workers to antineoplastic agents can lead to genotoxic damage. However, we observed a lack of data on exposure as well as genotoxic and epigenetic effects in workers other than healthcare workers. Furthermore, gaps in the current knowledge regarding the potential epigenetic effects caused by antineoplastic drug exposure and regarding the link between internal antineoplastic drug concentration and genotoxic and epigenetic effects after occupational exposure to antineoplastic agents were identified, offering a first step for future research. [ABSTRACT FROM AUTHOR]

Aims: : To determine whether the blood–brain barrier (BBB) opens to enhance drug delivery during the acute stage of unsaturated fat embolism. Methods: : We infused oleic, linoleic, and linolenic acid emulsions through the right common carotid artery of rats, followed by trypan blue for gross and lanthanum for electron microscopic (EM) examination. Doxorubicin and temozolomide were also administered, and then the rats were euthanized at 30 min, 1 h, and 2 h. Trypan blue hue was analyzed to semiquantitatively measure BBB opening. Desorption electrospray ionization–mass spectrometry (DESI–MS) imaging was used to evaluate drug delivery. Results: Trypan blue staining observed in each group 30 min after emulsion infusion increased at 1 h and decreased after 2 h in the oleic acid group. The linoleic and linolenic acid groups showed weak staining over time. The hue and trypan blue analysis results were corroborative. EM showed tight junction opening, whereas DESI–MS imaging showed increased doxorubicin and temozolomide signal intensities in ipsilateral hemispheres of all three groups. Conclusion: We demonstrated that oleic, linoleic, and linolenic acid emulsions opened the BBB, promoting drug delivery to the brain. Hue analysis and DESI–MS imaging are appropriate for analysis of doxorubicin and temozolomide concentrations in brain tissue. [ABSTRACT FROM AUTHOR]

To evaluate the effects of safe‐handling education on the cognition, practice and stress handling of antineoplastic drugs in clinical nurses. This study uses a quasi‐experimental, non‐equivalent control group pre‐test and post‐test design. The experimental and control groups had 30 nurses each, who handled antineoplastic drugs from three institutions. This study examines the safe handling of antineoplastic drugs six times, for two hours each over two weeks. To verify the homogeneity of the experimental and control groups and the effectiveness of safe‐handling education about antineoplastic drugs, a chi‐square test and independent samples t‐test were performed. The results were statistically significant in both groups (cognition [t = 6.84, p < 0.001], practice [t = 5.86, p < 0.001], and the stress of handling antineoplastic drugs [t = 5.15, p < 0.001]). Education on ways to safely handle antineoplastic drugs improves cognition, practice and stress handling of these drugs; moreover, proper education minimizes exposure. [ABSTRACT FROM AUTHOR]

Background Each country manages access to anticancer drugs differently due to variations in the structure and financing of the health system, but a summary of the various strategies used is absent. This study aimed to review and summarize financing strategies implemented across countries to facilitate access to high-cost anticancer drugs. Methods We conducted a systematic review of articles referenced in PubMed, Embase, and Web of Science through May 12, 2021. Articles published in the English language from 2000 that describe strategies implemented in different countries to facilitate access to high-cost anticancer drugs were included. Letters, news articles, and proposed strategies were excluded. Quality assessment was not performed as we aimed to summarize the strategies. Data were analyzed by thematic analysis. A review protocol was registered at PROSPERO (CRD42018068616).Results The review included 204 studies from 176 countries. Three themes of financing strategies were identified: (1) Basic pharmaceutical reimbursement and pricing policies, (2) Alternative funding strategies specific to high-cost drugs, and (3) Financial assistance for individual patients. Access in most countries depends mainly on basic pharmaceutical reimbursement policies (165 of 176 countries). Apart from that, high-income countries (HICs) tended to use funding strategies targeting high-cost drugs (72% of HICs vs 0%-24% of the rest), such as managed entry agreements (MEAs) or dedicated funds for high-cost drugs. In contrast, lower-income countries tended to implement financial assistance programs for cancer patients as a tool to increase access (32% of HICs vs 62%-79% of the rest).Conclusion Many countries have implemented a combination of strategies to increase access to high-cost anticancer drugs. Most low- and middle-income countries utilized placement of anticancer drugs on a national list of essential medicines and patient assistance programs (PAPs) to facilitate access, while many HICs implemented a broader range of strategies.

Abstract Aims : To determine whether the blood–brain barrier (BBB) opens to enhance drug delivery during the acute stage of unsaturated fat embolism. Methods : We infused oleic, linoleic, and linolenic acid emulsions through the right common carotid artery of rats, followed by trypan blue for gross and lanthanum for electron microscopic (EM) examination. Doxorubicin and temozolomide were also administered, and then the rats were euthanized at 30 min, 1 h, and 2 h. Trypan blue hue was analyzed to semiquantitatively measure BBB opening. Desorption electrospray ionization–mass spectrometry (DESI–MS) imaging was used to evaluate drug delivery. Results Trypan blue staining observed in each group 30 min after emulsion infusion increased at 1 h and decreased after 2 h in the oleic acid group. The linoleic and linolenic acid groups showed weak staining over time. The hue and trypan blue analysis results were corroborative. EM showed tight junction opening, whereas DESI–MS imaging showed increased doxorubicin and temozolomide signal intensities in ipsilateral hemispheres of all three groups. Conclusion We demonstrated that oleic, linoleic, and linolenic acid emulsions opened the BBB, promoting drug delivery to the brain. Hue analysis and DESI–MS imaging are appropriate for analysis of doxorubicin and temozolomide concentrations in brain tissue.

Background: Recent studies highlighted the functional role of protein arginine methyltransferases (PRMTs) catalyzing the methylation of protein arginine in malignant progression of various tumors. Stratification the subtypes of hepatocellular carcinoma (HCC) is fundamental for exploring effective treatment strategies. Here, we aim to conduct a comprehensive analysis of PRMTs with bioinformatic tools to identify novel biomarkers for HCC subtypes classification and prognosis prediction, which may be potential ideal targets for therapeutic intervention.Methods: The expression profiling of PRMTs in HCC tissues was evaluated based on the data of TCGA-LIHC cohort, and further validated in HCC TMA cohort and HCC cell lines. HCC was systematically classified based on PRMT family related genes. Subsequently, the differentially expressed genes (DEGs) between molecular subtypes were identified, and prognostic risk model were constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression analysis to evaluate the prognosis, gene mutation, clinical features, immunophenotype, immunotherapeutic effect and antineoplastic drug sensitivity of HCC.Results: PRMTs expression was markedly altered both in HCC tissues and HCC cell lines. Three molecular subtypes with distinct immunophenotype were generated. 11 PRMT-related genes were enrolled to establish prognostic model, which presented with high accuracy in predicting the prognosis of two risk groups in the training, validation, and immunotherapy cohort, respectively. Additionally, the two risk groups showed significant difference in immunotherapeutic efficacy. Further, the sensitivity of 72 anticancer drugs was identified using prognostic risk model.Conclusion: In summary, our findings stratified HCC into three subtypes based on the PRMT-related genes. The prognostic model established in this work provide novel insights into the exploration of related therapeutic approaches in treating HCC.

A novel and robust electrochemical sensing tool for the determination of vismodegib (VIS), an anticancer drug, has been developed by integrating the selective recognition capabilities of molecularly imprinted polymer (MIP) and the sensitivity enhancement capability of metal-organic framework (MOF). Prior to this step, the electrochemical behavior of VIS was investigated using a bare glassy carbon electrode (GCE). It was observed that in 0.5 M H 2 SO 4 solution as electrolyte, VIS has an oxidation peak around 1.3 V and the oxidation mechanism is diffusion controlled. The determination of VIS in a standard solution using a bare GCE showed a linear response in the concentration range from 2.5 μM to 100 μM, with a limit of detection (LOD) of 0.75 μM. Since sufficient sensitivity and selectivity could not be achieved with bare GCE, a MIP sensor was developed in the next step of the study. For this purpose, the GCE surface was first modified by drop casting with as-synthesized Co-MOF. Subsequently, a MIP network was synthesized via a thermal polymerization approach using 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as monomer and VIS as template. MOFs are ideal electrode materials due to their controllable and diverse morphologies and modifiable surface properties. These characteristics enable the development of MIPs with more homogeneous binding sites and high affinity for target molecules. Integrating MOFs could help the performance of sensors with the desired stability and reproducibility. Electrochemical analysis revealed an observable enhancement of the output signal by the incorporation of MOF molecules, which is consistent with the sensitivity-enhancing role of MOF by providing more anchoring sites for the attachment of the polymer texture to the electrode surface. This MOF-MIP sensor exhibited impressive linear dynamic ranges ranging from 0.1 to 1.0 pM for VIS, with detection limits in the low picomolar range. In addition, the MOF-MIP sensor offers high accuracy, selectivity and precision for the determination of VIS, with no interference observed from complex media of serum samples. Additionally, in this study, Analytical GREEnness metric (AGREE), Analytical GREEnness preparation (AGREEprep) and Blue Applicability Grade Index (BAGI) were used to calculate the green profile score. [Display omitted] • Electrochemical behavior investigation of VIS on bare GCE for the first time. • Synthesis and detailed characterization of Co-MOF by XRD, XPS, FTIR, and SEM. • Design of a Co-MOF integrated MIP-based electrochemical sensor for the first time. • Highly selective and sensitive analysis of VIS in standard solution and serum. [ABSTRACT FROM AUTHOR]

Background: Each country manages access to anticancer drugs differently due to variations in the structure and financing of the health system, but a summary of the various strategies used is absent. This study aimed to review and summarize financing strategies implemented across countries to facilitate access to high-cost anticancer drugs. Methods: We conducted a systematic review of articles referenced in PubMed, Embase, and Web of Science through May 12, 2021. Articles published in the English language from 2000 that describe strategies implemented in different countries to facilitate access to high-cost anticancer drugs were included. Letters, news articles, and proposed strategies were excluded. Quality assessment was not performed as we aimed to summarize the strategies. Data were analyzed by thematic analysis. A review protocol was registered at PROSPERO (CRD42018068616). Results: The review included 204 studies from 176 countries. Three themes of financing strategies were identified: (1) Basic pharmaceutical reimbursement and pricing policies, (2) Alternative funding strategies specific to high-cost drugs, and (3) Financial assistance for individual patients. Access in most countries depends mainly on basic pharmaceutical reimbursement policies (165 of 176 countries). Apart from that, high-income countries (HICs) tended to use funding strategies targeting high-cost drugs (72% of HICs vs 0%-24% of the rest), such as managed entry agreements (MEAs) or dedicated funds for high-cost drugs. In contrast, lower-income countries tended to implement financial assistance programs for cancer patients as a tool to increase access (32% of HICs vs 62%-79% of the rest). Conclusion: Many countries have implemented a combination of strategies to increase access to high-cost anticancer drugs. Most low- and middle-income countries utilized placement of anticancer drugs on a national list of essential medicines and patient assistance programs (PAPs) to facilitate access, while many HICs implemented a broader range of strategies. [ABSTRACT FROM AUTHOR]

Summary: Background The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) was established in 2004. Since then, various pieces of legislation, notices, and guidelines have been issued, and the regulatory approval pathways for domestic drugs have been diversified. However, the effects of these measures have not been fully examined. We examined the impact of these measures on the approval of antineoplastic drugs and the design of pivotal clinical trials for efficacy assessment by the PMDA. Methods We collected data on the antineoplastic drugs approved by the PMDA in fiscal years 2004–2019. We extracted the approval review pathways and the pivotal clinical trial designs from the PMDA review reports, and analyzed them to identify patterns. Results In total, 387 indications in oncology were approved by the PMDA in fiscal years 2004–2019, or 365 indications excluding multiple regulatory pathways. The number of approved indications generally increased year on year (p < 0.001). The largest number of approved indications was under the Orphan Drug Designation (31%, 114/365) and this continues to increase (p < 0.001). In the 288 indications for which clinical trial data were submitted for review, the pivotal clinical trial designs changed significantly (p < 0.001) after the guideline on clinical evaluation for antineoplastic drugs was revised in 2006. Conclusion The number of indications in oncology approved by the PMDA has been increasing over the past 16 years, alongside changes in regulatory pathways. The 2006 guideline on clinical evaluation had a particular impact on pivotal clinical trial designs. [ABSTRACT FROM AUTHOR]

Resulted from the severe side effects, the development of inexpensive, simple and sensitive method for amethopterin (ATP, an antineoplastic drug) is very important but it still remains a challenge. In this work, low cost nanohybrid composed of carbon nanobowl (CNB) and β-cyclodextrins (β-CD) (CNB-CD) was prepared with a simple autopolymerization way and applied as electrode material to develop a novel electrochemical sensor of ATP. Scanning-/transmission-electron microscopy, Fourier transform infrared spectrum, photographic image and electrochemical technologies were utilized to characterize morphologies and structure of the as-prepared CNB and CNB-CD materials. On the basic of the coordination advantages from CNB (prominent electrical property and surface area) and β-CD (superior molecule-recognition and solubility capabilities), the CNB-CD nanohybrid modified electrode exhibits superior sensing performances toward ATP, and a low detection limit of 0.002 μM coupled with larger linearity of 0.005-12.0 μM are obtained. In addition, the as-prepared sensor offers desirable repeatability, stability, selectivity and practical application property, confirming that this proposal may have important applications in the determination of ATP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

A dual functional platform based on nickel ferrite (NF) modified magnetically retrievable 2D metal free g-Carbon Nitride (CN), with varied ratios of NF, was easily fabricated via sonication-calcination strategy and successfully employed for photocatalytic degradation as well as fluorescence sensing of antineoplastic drug, Doxorubicin as well as organophosphate pesticide, Chlorpyrifos for the first time. [Display omitted] • Multifunctional platform of magnetically retrievable g-C 3 N 4 was fabricated. • Profound photocatalytic activity for antineoplastic drug, doxorubicin was observed. • Direct Z-scheme led to effective charge separation and visible light absorption. • Selective and sensitive detection of toxic pesticide chlorpyrifos and doxorubicin. • Excellent analytical performance for detection of analytes in real water samples. With the goal to detect, quantify and remove virulent toxins for water decontamination, a dual functional platform based on nickel ferrite (NF) modified magnetically retrievable 2D metal free g-Carbon Nitride (CN), with varied ratios of NF, was fabricated via simple sonication-calcination route. The % degradation of antineoplastic drug, doxorubicin (DXR) were obtained to be 69.8 %, 49.1 %, 71.1 %, 85.4 %, 94.2 %, 88.5 % and 81.7 % for CN, NF, 2-CNNF, 4-CNNF, 6-CNNF, 8-CNNF and 10-CNNF, respectively with corresponding rate constant values of 0.069, 0.047, 0.075, 0.100, 0.148, 0.113 and 0.078 min−1. CNNF heterostructure displayed outstanding photocatalytic performance with 6-CNNF heterostructure displaying highest rate kinetics with rate constant value 2.2 and 3.2 times greater than pure CN and NF, respectively. The charge transfer occurring in CNNF heterostructure followed direct Z-scheme mechanistic pathway, which proffers two advantages of high photoinduced charge carriers separation and optimized redox capacity of binary system. UV–vis DRS, XPS and PL results supported the proposed mechanism. Radical scavenging experiments further validated the role of •O 2 −, h+ and HO• radicals in degrading target pollutant. Moreover, the fabricated material was efficiently employed as selective and sensitive sensor for fluorescence detection of pesticide, chlorpyrifos (CPF) and DXR with respective LOD values of 4.1 µM in the range of 5 µM to 100 µM and 1.6 µM in the range of 0.1 µM to 40 µM. Real world applicability was established by monitoring CPF and DXR in real water samples. This study presents the designing of multi-functional platform, exhibiting excellent optical as well as physical characteristics, for monitoring and obliteration of noxious pollutants in aqueous environment. [ABSTRACT FROM AUTHOR]

Background: The incidence of neoplasm has significantly increased around the world over the last decades, resulting in use of anti-neoplastic drugs and the potential for occupational exposure to these drugs. One of the most commonly used chemotherapeutic drugs for treatment of malignancies is 5-fluorouracil (5-FU). Objectives: In this study, in order to develop an appropriate adsorbent for selective extraction of ultra-trace 5-fluorouracil from urine samples, molecularly imprinted membranes (MIMs) of 5-FU were prepared by encapsulating molecularly imprinted polymer nanoparticles (MIP-NPs) into the electrospun polyethylene terephthalate (PET) nanofibers. Methods: The MIP-NPs encapsulated into electrospun PET nano-fibers were prepared by precipitation polymerization technique. These MIMs were used as selective sorbents for solid-phase extraction (SPE) of ultra-trace 5-FU from different samples prior to the analysis by high performance liquid chromatography (HPLC). Central Composite Design (CCD) was used for optimization of effective parameters in sorption and desorption steps of the molecularly imprinted membrane solid phase extraction (MIMSPE). Results: The optimum operating conditions for the proposed method were pH: 6.2, amount of sorbent: 10.3 mg and absorption time: 20.5 h, the volume of eluent: 1 mL, the composition of elution solvent: the ratio of 90.3:9.7 methanol and acetic acid, and desorption time: 1.27 h. Under these optimized conditions, the limit of detection for 5-FU by MIMSPE was 0.07 μ L-1. The recoveries of 5-FU from urine sample ranged from 92.95±3.85 to 94.85±2.85%. Conclusion: The proposed MIMSPE-HPLC method can potentially be applied for selective detection of 5-FU in real samples with no special sample pretreatment steps. [ABSTRACT FROM AUTHOR]

Cytostatics are toxic pharmaceuticals, whose presence in surfaces puts healthcare workers at risk. These drugs might also end up in hospital effluents (HWW), potentially damaging aquatic ecosystems. Bicalutamide is a cytostatic extensively consumed worldwide, but few analytical methods exist for its quantification and most of them require advanced techniques, such as liquid chromatography mass spectrometry (LC-MS), which are very complex and expensive for large monitoring studies. Therefore, a simple but reliable multi-matrix high performance liquid chromatographic method, with fluorescence detection, was developed and validated to rapidly screen abnormal concentrations of bicalutamide in HWW and relevant contamination levels of bicalutamide in indoor surfaces (>100 pg/cm2), prior to confirmation by LC-MS. The method presents good linearity and relatively low method detection limits (HWW: 0.14 ng/mL; surfaces: 0.28 pg/cm2). Global uncertainty was below 20% for concentrations higher than 25 ng/mL (HWW) and 50 pg/cm2 (surfaces); global uncertainty was little affected by the matrix. Therefore, a multi-matrix assessment could be achieved with this method, thus contributing to a holistic quantification of bicalutamide along the cytostatic circuit. Bicalutamide was not detected in any of the grab samples from a Portuguese hospital, but an enlarged sampling is required to conclude about its occurrence and exposure risks.

A body of research demonstrates examples of in vitro and in vivo synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence for future novel combination therapies for cancer treatment, we assess the targetable space of natural products using public domain compound-target information. When considering pathways from the Reactome database targeted by natural products, we found an increase in coverage of 61% (725 pathways), relative to pathways covered by FDA approved cancer drugs collected in the Cancer Targetome, a resource for evidence-based drug-target interactions. Not only is the coverage of pathways targeted by compounds increased when we include natural products, but coverage of targets within those pathways is also increased. Furthermore, we examined the distribution of cancer driver genes across pathways to assess relevance of natural products to critical cancer therapeutic space. We found 24 pathways enriched for cancer drivers that had no available cancer drug interactions at a potentially clinically relevant binding affinity threshold of < 100nM that had at least one natural product interaction at that same binding threshold. Assessment of network context highlighted the fact that natural products show target family groupings both distinct from and in common with cancer drugs, strengthening the complementary potential for natural products in the cancer therapeutic space. In conclusion, our study provides a foundation for developing novel cancer treatment with the combination of drugs and natural products.

Cancer is a broad term for a set of disorders marked by the development of physically and functionally changed cells that proliferate uncontrollably, infect neighboring tissues, and result in malignant tumours, 'neoplasm'. Cancer remains a difficult disease to treat because of the significant adverse effects and poor pharmacokinetic profile of antineoplastic drugs, despite advancements in our understanding of the features and behavior of tumor cells in recent decades. In this series, the role of natural polymers is prominent as a component of a novel delivery system of anticancer drugs. These natural polymeric drug delivery systems (NPDDS) have many advantages over synthetic polymers like controlled delivery, biodegradability, inexpensive, low toxicity profile, and easily obtainable. These polymers further modify for the targeting of tumour cells. This review discusses and critically analyses the different natural polymers, such as chitosan, cellulose, starch, albumin, dextran, fucoidan, gelatin, etc., in terms of natural ingredient-based polymeric nanocarriers specifically for cancer therapy. It also describes benefits, drawbacks, and opinions and provides insights about the efficacy of NPDDS as well as its future perspectives and tabulated recent patents and cases under clinical trials exploited for cancer treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nowadays, enzyme-mediated processes offer an eco-friendly and efficient alternative to the traditional multistep and environmentally harmful chemical processes. Herein we report the enzymatic synthesis of cladribine by a novel 2′-deoxyribosyltransferase (NDT)-based combined biocatalyst. To this end, Lactobacillus delbrueckii NDT (LdNDT) was successfully immobilized through a two-step immobilization methodology, including a covalent immobilization onto glutaraldehyde-activated biomimetic silica nanoparticles followed by biocatalyst entrapment in calcium alginate. The resulting immobilized derivative, SiGPEI 25000-LdNDT-Alg, displayed 98% retained activity and was shown to be active and stable in a broad range of pH (5–9) and temperature (30–60 °C), but also displayed an extremely high reusability (up to 2100 reuses without negligible loss of activity) in the enzymatic production of cladribine. Finally, as a proof of concept, SiGPEI 25000-LdNDT-Alg was successfully employed in the green production of cladribine at mg scale.

A body of research demonstrates examples of in vitro and in vivo synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence for future novel combination therapies for cancer treatment, we assess the targetable space of natural products using public domain compound-target information. When considering pathways from the Reactome database targeted by natural products, we found an increase in coverage of 61% (725 pathways), relative to pathways covered by FDA approved cancer drugs collected in the Cancer Targetome, a resource for evidence-based drug-target interactions. Not only is the coverage of pathways targeted by compounds increased when we include natural products, but coverage of targets within those pathways is also increased. Furthermore, we examined the distribution of cancer driver genes across pathways to assess relevance of natural products to critical cancer therapeutic space. We found 24 pathways enriched for cancer drivers that had no available cancer drug interactions at a potentially clinically relevant binding affinity threshold of < 100nM that had at least one natural product interaction at that same binding threshold. Assessment of network context highlighted the fact that natural products show target family groupings both distinct from and in common with cancer drugs, strengthening the complementary potential for natural products in the cancer therapeutic space. In conclusion, our study provides a foundation for developing novel cancer treatment with the combination of drugs and natural products. [ABSTRACT FROM AUTHOR]

Abstract Cyclophosphamide (Cyc) and 5-fluorouracil (5-FU) are two of the most used antineoplastic drugs (AD) in the world. However, their discharge in the environment became a yet-unknown environmental issue that has impact on some groups of animals, such as amphibians. We assessed tadpoles (Lithobates catesbeianus) exposed to environmental concentrations (EC) of Cyc and 5-FU to evaluate whether they can cause morphological and mutagenic changes in them. We defined the following groups: control, positive control (50 mg/L of Cyc), EC-Cyc-I (0.2 μg/L), EC-Cyc-II (0.5 μg/L), EF-Cyc (2.0 μg/L), EC-5-FU-I (13.0 μg/L), EC-5-FU-II (30.4 μg/L) and EF-5-FU (123.5 μg/L). EC groups presented predictive AD concentrations in 10% and 25% hospital-effluent dilutions in water. EF groups met gross hospital-effluent concentrations. Based on our data, ADs caused intestinal changes and influenced the interocular distance in tadpoles after 30-day exposure. We also observed the aneugenic and clastogenic effect of ADs due to the higher frequency of micronucleated and binucleated erythrocytes, and blebbed, multilobulated, notched and kidney-shaped nuclei in animals exposed to them. Based on such changes, we assume that Cyc and 5-FU can trigger malignant cell transformation processes, and cancer, in animals exposed to them, even at low concentrations. Our study is the first to describe that Cyc and 5-FU, spread in the environment, cause damages in non-target organisms opposite to their original end. Graphical abstract Unlabelled Image Highlights • Toxicity of antineoplastic drugs in tadpoles • Cyclophosphamide (Cyc) and 5-fluorouracil (5-FU) induced morphological changes in tadpole. • Cyc and 5-FU cause mutagenic effects on L. catesbeianus tadpoles. [ABSTRACT FROM AUTHOR]

Aim: Cancer drugs have become prohibitive, and consequently their accessibility has increasingly been of great concern in many countries. Particularly, the information about cancer drug access in Thailand has been sporadic. Therefore, the goal of the study was to examine the antineoplastic drug accessibility in Thailand in terms of both market access and patient access. In addition, this study evaluated antineoplastic drugs based on cancer incidence in Thailand, and especially those for the top 3 common cancer types: Breast cancer, colorectal cancer, and lung cancer. Method: The study method was descriptive in nature to evaluate the number of antineoplastic drugs in both Thai market and reimbursement list or National List of Essential Medicines to reflect the market access and patient access, respectively. In determining Thailand's market access, the number of active ingredients (APIs) of antineoplastic drugs was obtained from the WHO website as a reference to the number of Thailand's marketing authorization approvals (MAAs) of antineoplastic drugs as per the Thai FDA website. For the determination of patient access, the number of antineoplastic drugs available to Thai patients was extracted from 2016 NLEM so that it can be compared to Thailand's MAAs. For further delineation with respect to treatments for each cancer type (ranked by cancer incidence in Thailand), the total number of APIs for each cancer type was used to determine market access and patient access. Results: The accessibility of antineoplastic drugs was 49% (88 of 180 APIs of WHO) for Thailand's market access and 43% (38 of 88 APIs in Thailand) for the patient access. For the top 3 cancer types, the market access was of a high percentage while the patient access from NLEM list was of low percentage. Conclusions: The market accessibility of antineoplastic drugs did not pose a problem for Thailand. Registrations of anti-cancer drugs undoubtedly played a key role for the market accessibility. However, new innovative antineoplastic drugs have presented a rather considerable concern for Thai patients, which are further complicated by the NLEM selection process and the limitation of use according to the categories outlined in the NLEM requirements. Therefore, improvement is clearly needed for patient access to new innovative antineoplastic drugs. [ABSTRACT FROM AUTHOR]

Cisplatin is a chemotherapeutic agent widely used for the treatment of solid cancers. Its administration is commonly associated with acute and chronic gastrointestinal dysfunctions, likely related to mucosal and enteric nervous system (ENS) injuries, respectively. Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone exerting trophic/reparative activities on the intestine, via antiapoptotic and pro-proliferating pathways, to guarantee mucosal integrity, energy absorption and motility. Further, it possesses anti-inflammatory properties. Presently, cisplatin acute and chronic damages and GLP-2 protective effects were investigated in the mouse distal colon using histological, immunohistochemical and biochemical techniques. The mice received cisplatin and the degradation-resistant GLP-2 analog ([Gly2]GLP-2) for 4 weeks. Cisplatin-treated mice showed mucosal damage, inflammation, IL-1β and IL-10 increase; decreased number of total neurons, ChAT- and nNOS-immunoreactive (IR) neurons; loss of SOX-10-IR cells and reduced expression of GFAP- and S100β-glial markers in the myenteric plexus. [Gly2]GLP-2 co-treatment partially prevented mucosal damage and counteracted the increase in cytokines and the loss of nNOS-IR and SOX-10-IR cells but not that of ChAT-IR neurons. Our data demonstrate that cisplatin causes mucosal injuries, neuropathy and gliopathy and that [Gly2]GLP-2 prevents these injuries, partially reducing mucosal inflammation and inducing ENS remodeling. Hence, this analog could represent an effective strategy to overcome colonic injures induced by cisplatin.

The inorganic antineoplastic drug cisplatin was made to react in solution with the dipeptide cysteinylglycine (CysGly), chosen as a functional model of glutathione, and the reaction products were analyzed using electrospray ionization mass spectrometry (ESI-MS). Selected complexes, i.e., the primary substitution product cis- [PtCl(NH 3) 2 (CysGly)]+ and the chelate cis- [PtCl(NH 3)(CysGly)]+, were submitted to IR multiple photon dissociation (IRMPD) spectroscopy obtaining their vibrational features. The experimental IR ion spectra were compared with the calculated IR absorptions of different plausible isomeric families, finding CysGly to bind preferentially platinum(II) via its deprotonated thiolic group in the monovalent complex, cis- [PtCl(NH 3) 2 (CysGly)]+, and to evolve in the S,N-bound chelate structure cis- [PtCl(NH 3)(CysGly)]+ through the SH and NH 2 functionality of the cysteine residue. Moreover, our findings indicate that the platination reaction does not affect the CysGly peptide bond, which remains in its trans configuration. These results provide additional insights into the reactivity of Pt(II)-complexes with glutathione which is involved in cellular cisplatin resistance. Cisplatin was allowed to react with cysteinylglycine, a dipeptide chosen as a model of glutathione. The substitution products cis -[PtCl(NH 3) 2 (CysGly)]+ and cis -[PtCl(NH 3)(CysGly)]+ were mass-selected and assayed by IRMPD spectroscopy backed by DFT calculations. Their vibrational and structural features were thoroughly investigated. [Display omitted] • ESI-MS allows the detection of monovalent CysGly substitution adduct with cisplatin. • Structures of the reaction products of cisplatin with CysGly have been determined. • CysGly binds with its thiolate function to platinum as a zwitterion. • Cisplatin interaction with the dipeptide does not alter the peptide group isomerism. [ABSTRACT FROM AUTHOR]

Internal contamination of healthcare professionals by antineoplastic drugs (ADs) remains a current occupational health issue, particularly because these compounds are classified as dangerous to handle by the NIOSH. In order to improve preventive actions, a study of the factors associated with this internal contamination was conducted among nursing staff in health care institutions. This study is a statistical analysis of metadata from a cross-sectional observational study conducted among nurses in two French hospitals. The internal contamination of each nurse was assessed in a previous study and was defined by whether or not at least one studied AD was detected in at least one urine sample. Three urine samples and a self-questionnaire were collected for each participant. Analysis of five ADs (cyclophosphamide, ifosfamide, metabolite of 5-fluorouracil, methotrexate, doxorubicin) were performed by liquid chromatography coupled to tandem mass spectrometry. A multivariate stepwise descending regression model was used to determine factors associated with internal contamination by coupling data from a self-questionnaire with internal contamination data. A total of 74 nurses participated to the study and 68 were included for this work: 39 nurses with and 29 without detectable internal ADs contamination. Two protective factors of internal contamination could be identified: a high "glove wearing score" (OR: 0.957; 95%CI: 0.93–0.98; p < 0.01) and a high "total number of years handling ADs and/or caring for patients treated with ADs" (OR: 0.797; 95%CI: 0.67–0.91; p < 0.01). In addition, three factors contributing to internal contamination were identified, namely "feeling sufficiently informed about tasks exposing to ADs" (OR: 9.585; 95%CI: 2.23–57.05; p < 0.01), "disposal of a waste bin containing equipment used for administration of the ADs studied" (OR: 8.04; 95%CI: 1.87–46.08; p < 0.01) and "changing sheets and/or making bed of a patient treated by one of the ADs studied" (OR: 10.479; 95%CI: 1.43–133.30; p < 0.05). Thus, the use of gloves when handling ADs directly or indirectly and the contaminating nature of certain tasks should be taken into account when (1) implementing preventive actions in health care services and (2) training and informing exposed staff. Further studies would be desirable to confirm these results and extend them to other professional categories. [ABSTRACT FROM AUTHOR]

Today the oncology nursing importance has been increased because of that cancer is one of the most important health problem in Turkey, as it is in the other countries throughout the world. By the way antineoplalastic drugs, which not only effect patients but also create negative effects on nurses, create negative working conditions for oncology nurses. The studies that compared nurses exposed to antineoplastic agents have been found the association between workplace explosure to antineoplastic and congenital malformations, ectopic pregnancies, miscarriages, stillbirths etc. In order to prevent all unwanted negative effects on effects, it has been necessary to develop standards and practice guidelines for preventive measures to be taken during the preperation and administration of antineoplastic drugs.

The aim of this study was to assess the ability of Raman spectroscopy to discriminate and quantify five antineoplastic drugs in an aqueous matrix at low concentrations before patient administration. Five antineoplastic drugs were studied at therapeutic concentrations in aqueous 0.9% sodium chloride: 5-fluorouracil (5FU), gemcitabine (GEM), cyclophophamide (CYCLO), ifosfamide (IFOS) and doxorubicin (DOXO). All samples were packaged in glass vials and analyzed using Raman spectrometry from 400 to 4000 cm − 1 . Discriminant analyses were performed using Partial Least Squares Discriminant Analysis (PLS-DA) and quantitative analyses using PLS regression. The best discrimination model was obtained using hierarchical PLS-DA models including three successive models for concentrations higher than the lower limit of quantification (0% of fitting and cross-validation error rate with an excellent accuracy of 100%). According to these hierarchical discriminative models, 90.8% (n = 433) of external validation samples were correctly predicted, 2.5% (n = 12) were misclassified and 6.7% (n = 32) of the external validation set were not assigned. The quantitative analysis was characterized by the RMSEP that ranged from 0.23 mg/mL for DOXO to 3.05 mg/mL for 5FU. The determination coefficient (R 2 ) was higher than 0.9994 for all drugs evaluated except for 5FU (R 2 = 0.9986). This study provides additional information about the potential value of Raman spectroscopy for real-time quality control of cytotoxic drugs in hospitals. In some situations, this technique therefore constitutes a powerful alternative to usual methods with ultraviolet (UV) detection to ensure the correct drug and the correct dose in solutions before administration to patients and to limit exposure of healthcare workers during the analytical control process. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Structural chromosomal aberrations in blood lymphocytes represent a biomarker for cellular damage caused by genotoxic carcinogens and are an indicator of increased cancer risk. We evaluated the association between frequencies of total chromosomal aberrations, chromatid- and chromosome-type aberrations, and occupational exposures to volatile anesthetics, antineoplastic agents, and formaldehyde among 601 medical professionals. METHODS: Chromosomal damage among exposed individuals and unexposed controls was determined by conventional cytogenetic analysis. We used binary logistic regression to evaluate the effects of workplace exposures and major confounders on chromosomal damage. RESULTS: Significantly higher frequencies of total chromosomal, chromatid-type and chromosome-type aberrations were observed among subjects occupationally exposed to volatile anesthetics, antineoplastic agents, and formaldehyde compared to age- and sex-matched controls (P

This review describes published high performance liquid chromatography/mass spectrometry (HPLC–MS) methods for the determination of anticancer drugs in human urine as non-invasive tool for monitoring of health care worker exposure to antineoplastic and cytotoxic drugs. HPLC–MS is a sensitive and specific method for analysis of anticancer drugs and their metabolites in biological fluids. In this review, a tabular summary and overview of published HPLC–MS methods are presented, as well as future trends and limitations in this area of research. [ABSTRACT FROM AUTHOR]